Fluorescence imaging of living cells is key to better understanding cellular morphology and biological processes. Water-dispersible nanoparticles exhibiting thermally activated delayed fluorescence (TADF) have recently emerged as useful probes for time-resolved fluorescence imaging (TRFI), circumventing interference from biological autofluorescence. Many existing approaches, however, require TADF dyes with specific structural features, precluding many high-performance TADF materials from being used in this application.
View Article and Find Full Text PDFDespite the innate ability for bone to remodel and repair, its regeneration has a limit. In these cases of critically sized bone defects (CSBD), the bone deficit must be repaired using reconstructive techniques that support immediate load bearing and encourage bone bridging across the defect. High-strength porous titanium implants offer a solution for treatment of CSBD in which the scaffold can support physiological loads, provide a matrix to guide ingrowth, and carry graft materials and/or biologics.
View Article and Find Full Text PDFBackground: Metallic reconstruction plates used for fracture stabilization typically require intraoperative contouring for patient-specific anatomical fit. Despite this, characterization of plate mechanical properties after contouring has previously been limited. The objective of this study was to assess whether contouring affects fatigue resistance for three types of Stryker seven-hole stainless steel (SS) 316LVM fracture fixation plates.
View Article and Find Full Text PDFInvestigating biophysical cellular interactions in the circulation currently requires choosing between in vivo models, which are difficult to interpret due in part to the hemodynamic and geometric complexities of the vasculature; or in vitro systems, which suffer from non-physiologic assumptions and/or require specialized microfabrication facilities and expertise. To bridge that gap, we developed an in vitro "do-it-yourself" perfusable vasculature model that recapitulates in vivo geometries, such as aneurysms, stenoses, and bifurcations, and supports endothelial cell culture. These inexpensive, disposable devices can be created rapidly (<2 hours) with high precision and repeatability, using standard off-the-shelf laboratory supplies.
View Article and Find Full Text PDFDespite its widespread clinical use in load-bearing orthopedic implants, polyether-ether-ketone (PEEK) is often associated with poor osseointegration. In this study, a surface-porous PEEK material (PEEK-SP) was created using a melt extrusion technique. The porous layer was 399.
View Article and Find Full Text PDFCharacterization of articular cartilage morphology and composition using microcomputed tomography (microCT) techniques requires the use of contrast agents to enhance X-ray attenuation of the tissue. This chapter describes the use of an anionic iodinated contrast agent at equilibrium with articular cartilage. In this technique, negatively charged contrast agent molecules distribute themselves inversely with respect to the negatively charged proteoglycans (PGs) within the cartilage tissue (Palmer et al.
View Article and Find Full Text PDFBone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C-C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss.
View Article and Find Full Text PDFSkeletal development and growth are complex processes regulated by multiple microenvironmental cues, including integrin-ECM interactions. The β1 sub-family of integrins is the largest integrin sub-family and constitutes the main integrin binding partners of collagen I, the major ECM component of bone. As complete β1 integrin knockout results in embryonic lethality, studies of β1 integrin function in vivo rely on tissue-specific gene deletions.
View Article and Find Full Text PDFThe objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups.
View Article and Find Full Text PDFNon-healing bone defects present tremendous socioeconomic costs. Although successful in some clinical settings, bone morphogenetic protein (BMP) therapies require supraphysiological dose delivery for bone repair, raising treatment costs and risks of complications. We engineered a protease-degradable poly(ethylene glycol) (PEG) synthetic hydrogel functionalized with a triple helical, α2β1 integrin-specific peptide (GFOGER) as a BMP-2 delivery vehicle.
View Article and Find Full Text PDFObjective: The goal of this report is to describe the outcome of sequential particulated cartilage allograft and autologous osteochondral transfer treatments for an osteochondral lesion of the medial femoral condyle.
Methods: A 44-year-old woman was treated with a particulated juvenile articular cartilage allograft (DeNovo NT) for a chondral lesion of the knee. As a result of continued pain, she had 2 further surgeries, including an autologous osteochondral transfer system procedure and finally a unicondylar knee arthroplasty.
Introduction: Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of μ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of μ-dHACM would attenuate OA progression.
View Article and Find Full Text PDFObjective: To assess temporal changes in cartilage and bone morphology, reactive oxygen species (ROS), and vascularization in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA), using advanced imaging methodologies.
Methods: Right knees of 8-week-old male Wistar rats were injected with 1 mg MIA in 50 μl saline and left knees were injected with 50 μl saline as controls. After 1, 2, and 3 weeks (n = 5 at each time point), changes in cartilage morphology and composition were quantified using equilibrium partitioning of an ionic contrast agent microfocal computed tomography (μCT), and changes in subchondral and trabecular bone were assessed by standard μCT.
Fracture healing is highly sensitive to mechanical conditions; however, the effects of mechanical loading on large bone defect regeneration have not been evaluated. In this study, we investigated the effects of functional loading on repair of critically sized segmental bone defects. About 6-mm defects were created in rat femora, and each defect received 5 µg recombinant human bone morphogenetic protein-2 (rhBMP-2), delivered in alginate hydrogel.
View Article and Find Full Text PDFSeveral studies have tested the strength and various fixation modalities of the long dorsal arm offset V osteotomy, and have proven it to be a stable construct when fixated properly. We believe that a modification of the traditional Austin cuts, with a slightly longer plantar arm, lends itself to greater stability because instead of ground reactive forces applying a distraction moment on the osteotomy, the ground actually compresses the osteotomy leading to greater stability and less chance of failure. We compared the mechanical stability of the long dorsal offset V osteotomy to the slightly longer plantar arm osteotomy using 20 sawbone models, 10 in each study group.
View Article and Find Full Text PDFThe primary purpose of this study was to determine if tibial bone strength is compromised in dystrophic mice and if so, what geometric and material properties contribute. Results of three-point bending tests showed that tibia of mdx and dko (dystrophin- and utrophin-deficient) mice had up to 50% lower strength and stiffness compared to wild-type mice. Micro-computed tomography indicated that dystrophic tibia had reductions of 6-57% in cortical cross-sectional moment of inertia and cross-sectional area.
View Article and Find Full Text PDFPurpose: In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye.
Methods: A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo.
Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
June 2010
Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Currently, limited technologies exist to encourage angiogenesis and arteriogenesis in a controlled manner. In the present study, we describe an injectable controlled release system consisting of VEGF encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs).
View Article and Find Full Text PDFAlthough the essential role of cyclooxygenase (COX)-2 in fracture healing is known, the targeted genes and molecular pathways remain unclear. Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture healing. In a fracture-healing model, COX-2(-/-) mice showed delayed initiation and impaired endochondral bone repair, accompanied by a severe angiogenesis deficiency.
View Article and Find Full Text PDFIt has long been known that the bone adapts according to the local mechanical environment. To date, however, a model for studying the effects of functional mechanical loading on tissue-engineered bone repair in vivo has not yet been established. We have developed a rat femoral defect model, in which ambulatory loads are transduced through the implanted tissue-engineered construct to elucidate the role of the mechanical environment in functional restoration of a large bone defect.
View Article and Find Full Text PDFAppropriate porosity is an important biomaterial design criterion for scaffolds used in tissue engineering applications as it can permit increased cell adhesion, migration, proliferation and extracellular matrix production within the scaffold at a tissue defect site. Tissue engineering scaffolds can either be injected in a minimally invasive manner or implanted through surgical procedures. Many injectable scaffolds are hydrogel-based; these materials often possess nanoscale porosity, which is suboptimal for cell migration and proliferation.
View Article and Find Full Text PDFPorous biomaterials designed to support cellular infiltration and tissue formation play a critical role in implant fixation and engineered tissue repair. The purpose of this Leading Opinion Paper is to advocate the use of high resolution 3D imaging techniques as a tool to quantify extracellular matrix formation and vascular ingrowth within porous biomaterials and objectively compare different strategies for functional tissue regeneration. An initial over-reliance on qualitative evaluation methods may have contributed to the false perception that developing effective tissue engineering technologies would be relatively straightforward.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
November 2007
The study's objective was to investigate how estrogen deficiency and run training affect the tibial bone-soleus muscle functional relationship in mice. Female mice were assigned into one of two surgical conditions, ovariectomy (OVX) or sham ovariectomy (sham), and one of two activity conditions, voluntary wheel running (Run) or sedentary (Sed). To determine whether differences observed between OVX and sham conditions could be attributed to estradiol (E(2)), additional OVX mice were supplemented with E(2).
View Article and Find Full Text PDFGrowth factors have been widely used in strategies to regenerate and repair diseased tissues, but current therapies that go directly from bench to bedside have had limited clinical success. We hypothesize that engineering successful therapies with recombinant proteins will often require specific quantitative information of the spatiotemporal role of the factors and the development of sophisticated delivery approaches that provide appropriate tissue exposures. This hypothesis was tested in the context of therapeutic angiogenesis.
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